Dr. Johnson is a junior faculty member in the Division of Neurology, Department of Medicine at Brigham and Women's Hospital, and Harvard Medical School. He intends to remain at Brigham and Women's Hospital for a considerable time and to become an independent investigator within the Hospital's Center for Neurologic Diseases. He is in the process of building on his extensive experience in the biochemistry and immunology of myelin, and applying it to the examination and manipulation of experimental autoimmune demyelinating disorders in experimental animals. The RCDA award would enable Dr.Johnson to have the personal support necessary to expand his research group, and to consolidate his basic studies on the cellular basis of demyelination. The Department of Medicine expects that Dr. Johnson will become an Associate professor during the period of the RCDA, and the Center for Neurologic Diseases within that Department anticipates that Dr. Johnson will become a fully independent member of the Center during this time. The Center represents a multidisciplinary group of scientists working on several neurological disorders, and provides a stimulating environment for the development of junior faculty. The RCDA project involves the study of the regulation of nervous system mast cells, and how they may contribute to inflammatory demyelination, and stems from the successful progress of a currently funded PHS grant. Dr. Johnson will conduct detailed studies of the role of myelin-specific IgE antibodies in demyelination, examining both endogenous and exogenous IgE. He will also expand on his preliminary findings of mast cell migration into the nervous system, and examine the effects of in situ mast cell degranulation on the myelin sheath. Finally, Dr. Johnson will use a variety of techniques to examine how manipulation of nervous system mast cells can effect disease progression. These will include drug treatment, ablation of the IgE response, and injection of lymphokines.